Mediating Effect of Body Mass Index and Dyslipidemia on the Relation of Uric Acid and Type 2 Diabetes: Results From China Health and Retirement Longitudinal Study

Abstract

ObjectiveThis study assessed temporal relationships of serum uric acid (SUA) with blood glucose and determine the mediating effects of body mass index (BMI) and dyslipidemia on the relation of SUA and risk of type 2 diabetes.MethodsParticipants aged ≥ 45 years were participated in 2011 and followed up until 2015. Cox proportional hazards regression with a robust variance estimator was performed to explore the association of SUA with the risk of diabetes, and crosslagged path analysis was introduced to examine the temporal relationships between SUA and blood glucose. A mediation analysis was finally used to identify the mediating effect of BMI and dyslipidemia on the relation of SUA and the future risk of diabetes.ResultsA total of 9,020 participants were included with an average age of 58.59 years at baseline in 2011, and 53.6% of them were women. Linear dose–response relationship was identified by restricted spline cubic analysis between baseline SUA and follow-up blood glucose (the non-linear trend for fasting plasma glucose (FPG): β2 = −0.71, p = 0.52; for HbA1c: β2 = 0.05, p = 0.07; for risk of diabetes: β2 = 0.12, p = 0.39). Additionally, compared with the lowest quartiles of SUA, the adjusted risk ratios of diabetes were 1.00 (95% CI: 0.82–1.23), 1.08 (95% CI: 0.89–1.31), and 1.37 (95% CI: 1.11–1.96) for quartile 2–4 (p-trend < 0.01), respectively. Further additional adjustments for BMI or dyslipidemia, these ratios were not statistically significant. In addition, a unidirectional relationship from baseline SUA to follow-up FPG (ρ1 = 0.24, p = 0.03) was further confirmed using crosslagged path analysis. After stratifying by genders, the above results were only significant in the women subgroup, and we thus conducted a mediation analysis in women and found that the BMI and dyslipidemia partially mediated the effect of SUA on diabetes with a 23.05 and 18.82% mediating effect, respectively.ConclusionsThese findings provide strong evidence that hyperuricemia preceded diabetes, and the effect of baseline SUA on follow-up type 2 diabetes was more pronounced among middle-aged and elderly Chinese women, especially in postmenopausal women, and this effect is partly mediated by BMI and dyslipidemia at baseline.

Fatty liver mediates the association of hyperuricemia with prediabetes and diabetes: a weighting-based mediation analysis

“…In contrast, among the Asian population, including the Chinese people, mixed results were revealed ( 8 – 11 ). Using the multinomial logistic regression model, we observed that hyperuricemia was an independent risk factor for prediabetes but not diabetes among adults (aged between 35 and 75 years).…”

“…SUA is related to BMI and diabetes, and obesity is considered a mediator in the association between hyperuricemia and diabetes ( 16 ). A recent study showed that high BMI and dyslipidemia significantly mediated the association in women ( 11 ). Elevated SUA is significantly associated with hyperlipidemia ( 19 ) and a higher percentage of fat accumulation in the liver ( 20 ).…”

“…Several studies identified high SUA as an independent risk factor for T2DM, particularly among the Western population ( 6 , 7 ); however, epidemiological studies reported conflicting results among the Asian population ( 8 – 10 ). For instance, recent cohort studies in China demonstrated that high SUA was linked to an increased risk of T2DM only in women ( 8 , 11 ).…”

“…A national health survey showed a significant association between elevated SUA levels and the increased prevalence of abdominal obesity, hypertriglyceridemia, and hyperglycemia in the US population ( 15 ). A previous study reported that obesity could significantly mediate the association between hyperuricemia and diabetes risk ( 16 ), and body mass index (BMI) and dyslipidemia were significant mediators in the association only in women ( 11 ). However, the causal relationship between hyperuricemia and prediabetes or diabetes has yet to be explored.…”

Spatiotemporal Analysis and Risk Assessment Model Research of Diabetes among People over 45 Years Old in China

“…Besides, compared with other chronic diseases, hypertension and dyslipidemia are more likely to lead to diabetes, and diabetes also likely leads to the occurrence of hypertension or dyslipidemia [ 51 , 52 , 53 ]. As the main component of metabolic syndrome, diabetes, hyperglycemia, and hyperlipidemia interconnect and influence each other, forming a complex framework of chronic diseases [ 54 ]. With the prolongation of the disease’s course, the patient’s body’s immune function becomes increasingly abnormal, the function of many systems is weakened, and multiple diseases are prone to occur.…”